Neo-antigens for the serological diagnosis of IgE-mediated drug allergic reactions to antibiotics cephalosporin, carbapenem and monobactam
Ontology highlight
ABSTRACT:
SUBMITTER: Pena-Mendizabal E
PROVIDER: S-EPMC7525514 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:New Delhi metallo-?-lactamase-1 exhibits a broad substrate profile for hydrolysis of the penicillin, cephalosporin and 'last resort' carbapenems, and thus confers bacterial resistance to nearly all ?-lactam antibiotics. Here we address whether the high catalytic efficiency for hydrolysis of these diverse substrates is reflected by similar sequence and structural requirements for catalysis, i.e., whether the same catalytic machinery is used to achieve hydrolysis of each class. Deep sequencing of randomized single codon mutation libraries that were selected for resistance to representative antibiotics reveal stringent sequence requirements for carbapenem versus penicillin or cephalosporin hydrolysis. Further, the residue positions required for hydrolysis of penicillins and cephalosporins are a subset of those required for carbapenem hydrolysis. Thus, while a common core of residues is used for catalysis of all substrates, carbapenem hydrolysis requires an additional set of residues to achieve catalytic efficiency comparable to that for penicillins and cephalosporins.
| S-EPMC6207675 | biostudies-literature
Project description:Although there is concern that food allergy reactions may negatively affect the natural history of food allergy, the impact of reactions on food-specific IgE (sIgE) levels or skin prick test (SPT) wheal size is unknown.To measure the effects of allergic reactions on SPT wheal size and sIgE concentrations to milk, egg, and peanut.Participants included 512 infants with likely milk or egg allergy enrolled in a multicenter observational study. Changes in sIgE level and SPT wheal size to milk, egg, and peanut were measured before and after oral food challenge (OFC) or accidental exposure for 377 participants.The median age of the cohort at the time of analysis was 8.5 years (67% males). There were no statistically significant changes in sIgE level or SPT wheal size after positive OFC to milk, egg, or peanut (n = 20-27 for each food). Change in sIgE level and SPT wheal size was measured after 446 and 453 accidental exposure reactions, respectively. The median change in sIgE level was a decrease of 0.33 kU(A)/L (P < .01) after milk and 0.34 kU(A)/L (P < .01) after egg reactions, but no other statistically significant changes in sIgE level or SPT wheal size were observed for milk, egg, or peanut. When we limited the analysis to only those participants who had diagnostic testing done within 6 months of an accidental exposure reaction, we found that peanut SPT wheal size increased by 1.75 mm (P < .01), but a significant increase was not noted when all participants with testing done within 12 months were considered.The results suggest that reactions from OFCs and accidental exposure are not associated with increases in sensitization among children allergic to milk, egg, or peanut.
| S-EPMC4789127 | biostudies-literature
Project description:BACKGROUND:Despite the recognition of food allergies as a significant cause of morbidity and a growing public health burden worldwide, there are no epidemiological studies addressing food sensitization and allergy in Jordan. OBJECTIVE:To conduct an epidemiological study that retrospectively analyzes sensitization data from 3463 patients with suspected immunoglobulin E (IgE)-mediated food allergic reactions who performed specific IgE tests in our laboratories in Jordan. METHODS:Specific IgE (s-IgE) tests were analyzed for patients who performed enzyme allegro-sorbent testing based on either self-reported food allergy or upon physician's request. RESULTS:2.3% of the analyzed samples were cross-reactive to carbohydrate determinants. A quarter of the patients were sensitized to one or more food allergens, with males having higher odds of being s-IgE positive. Furthermore, a higher prevalence of sensitization was seen in infants and children compared with adults. s-IgE was most frequently found against cow milk (11.2%), pistachio (4.9%), soybean (4.6%), cherry (4.4%), and orange (4.4%). Interestingly, the s-IgE class distribution profile of pistachio differed from the rest of the top hits being skewed away from the weak class 1 leaning more towards higher IgE classes. Food allergen sensitization was age group-dependent: milk, tree nuts, and eggs were the main food groups causing sensitization in infants, while it was fruits followed by milk in children and adults. CONCLUSIONS:Our work represents the first epidemiological study addressing food sensitization in Jordan. This study lays a solid foundation for future studies that can help better guide food allergy diagnosis, patient dietary modifications, and food elimination plans, as well as assist decision-makers in the region to develop national strategies for an efficient and sustainable healthcare system.
| S-EPMC7416048 | biostudies-literature
Project description:Eucalyptus oil has been used since ancient times for its bactericidal, anti-inflammatory, analgesic and sedative effects. In recent years, the action of Eucalyptus oil has been scientifically proven, and there have been reports that Eucalyptus oil suppresses the production of chemokines, cytokines and lipid mediators in basophils, alveolar macrophages and monocytes. Based on this information, we aimed to verify whether Eucalyptus oil can be used for allergic dermatitis, the incidence of which has been increasing among human skin diseases. This effect was verified using a mouse IgE-mediated local allergic model. In conclusion, topical application of Eucalyptus oil suppressed oedema and vascular permeability enhancement due to IgE-mediated allergic on the skin. In addition, we also verified the degranuration of mast cells, which is a part of its action, and examined whether 1,8-cineole, which is the main component of Eucalyptus oil, suppresses the phosphorylation of PLCγ and p38 directly or indirectly. 1,8-cineole was found to suppress degranulation of mast cells.
| S-EPMC7708995 | biostudies-literature
Project description:Total serum IgE result from the combination of specific and non-specific pools. High specific/total IgE ratio may reflect high level of allergen-specific IgE on mast cells. No data regarding its applications to drug allergies is available. One hundred seventy-one patients with a history of immediate reactions to ?-lactams, confirmed by positive skin testing, and 122 control subjects tolerant to ?-lactams, were studied. CAP System was used for the detection of serum total and specific IgE antibodies. The specific/total IgE ratio was tested for diagnostic accuracy compared with conventional criteria. We finally performed a simulation study to expand our investigation of the performance of the specific/total IgE ratio index in a scenario in which the new CAP detection threshold is lowered further. Specific/total IgE ratio values ?0.002 were observed more frequently in reactive than in controls. Seventy-four of 80 subjects with values ?0.002 were allergic to ?-lactams, yielding a positive predictive value of 92.5%. The application of specific/total IgE ratio significantly improves the positive likelihood ratio and the overall diagnostic performance. In addition, we showed the capability of this new criterion to identify true reactive patients even among subjects with high levels of total IgE (>200 kU/L). Significant increase in both receiver operator characteristic (ROC) curve and sensitivity were observed in imputed case of the simulation study. The ?-lactams-specific/total IgE ratio may be an additional index compared to the common criterion of positivity to a single hapten in the allergological work-up of patients with ?-lactams immediate adverse reactions.
| S-EPMC4399843 | biostudies-literature
Project description:Radiation therapy remains a significant therapeutic modality in the treatment of cancer. An attractive strategy would be to enhance the benefits of ionizing radiation (IR)with radiosensitizers. A high-content drug repurposing screen of approved and investigational agents, natural products and other small molecules has identified multiple candidates that blocked repair of IR damage in vitro. Here, we validated a subset of these hits in vitro and then examined effects on tumor growth after IR in a murine tumor model. Based on robust radiosensitization in vivo and other favorable properties of cephalexin, we conducted additional studies with other beta-lactam antibiotics. When combined with IR, each cephalosporin tested increased DNA damage and slowed tumor growth without affecting normal tissue toxicity. Our data implicate reactive oxygen species in the mechanism by which cephalosporins augment the effects of IR. This work provides a rationale for using commonly prescribed beta-lactam antibiotics as non-toxic radiosensitizers to enhance the therapeutic ratio of radiotherapy.
| S-EPMC5085128 | biostudies-literature
Project description:Immunoglobulin E (IgE) plays a central role in the pathogenesis of Type I hypersensitivity through interaction with a high-affinity receptor (Fc?RI?). For therapeutic applications, substantial attention has been focused recently on the blockade of the IgE interaction with Fc?RI?. While exploring better options for preventing allergic diseases, we found that the Fab fragment of the rat anti-murine IgE antibody (Fab-6HD5) strongly inhibited passive cutaneous anaphylaxis (PCA) in vivo, as well as spleen tyrosine kinase (Syk) activity and ?-hexosaminidase release from basophilic leukemia cells in vitro. The in vivo effects of Fab-6HD5 pre-administration were maintained over a long period of time for at least 10 days. Using flow cytometry analysis, we also found that Fab-6HD5 did not recognize the IgE C?3 domain containing specific binding sites for Fc?RI?. Furthermore, deletion-mapping studies revealed that Fab-6HD5 recognized conformational epitopes on the C?2 domain of IgE. Given that the C?2 domain plays a key role in stabilizing the interaction of IgE with FcRI?, our results suggest that the specific binding of Fab-6HD5 to the C?2 domain prevents allergic reactions through destabilizing the preformed IgE-Fc?RI? complex on rat mast cells. Although the present study was performed using animal models, these findings support the idea that a certain antibody directed against IgE CH domains may contribute to preventing allergic diseases through interacting with IgE-Fc?RI? complex.
| S-EPMC6155129 | biostudies-literature
Project description:PurposeThe prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students.Methods131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM).ResultsIn serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy.ConclusionsNasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.Study identifier at ClinicalTrials.gov: NCT02810535.
| S-EPMC7322186 | biostudies-literature
Project description:Allergic diseases are inflammatory disorders that involve many types of cells and factors, including allergens, immunoglobulin (Ig)E, mast cells, basophils, cytokines and soluble mediators. Among them, IgE plays a vital role in the development of acute allergic reactions and chronic inflammatory allergic diseases, making its control particularly important in the treatment of IgE-mediated allergic diseases. This review provides an overview of the current state of IgE targeted therapy development, focusing on three areas of translational research: IgE neutralization in blood; IgE-effector cell elimination; and IgE+ B cell reduction. IgE-targeted medicines such as FDA approved drug Xolair (Omalizumab) represent a promising avenue for treating IgE-mediated allergic diseases given the pernicious role of IgE in disease progression. Additionally, targeted therapy for IgE-mediated allergic diseases may be advanced through cellular treatments, including the modification of effector cells.
| S-EPMC6050685 | biostudies-literature
Project description:Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid mainly found in fish oil. Although several studies have suggested that it can alleviate allergy symptoms, its mechanism of action remains to be elucidated. In the present study, we found that docosahexaenoyl ethanolamide (DHEA), a metabolite of DHA produced in the human body, exerts the anti-allergic activity in vitro and in vivo. DHEA suppressed degranulation of rat basophilic leukemia RBL-2H3 cells and bone marrow-derived mast cells in a dose-dependent manner without cytotoxicity. This occurred due to a decrease in Ca2+ influx, which is critical for mast cell degranulation. DHEA also suppressed IgE-mediated passive cutaneous anaphylaxis reaction in mice. In addition, DHEA was demonstrated to lessen an allergic symptom in a mouse model of pollinosis and to alter the production of IgE and cytokines secreted by splenocytes collected from the pollinosis mice. Taken together, this study indicates that DHEA is a promising anti-allergic agent as it inhibits mast cell degranulation and modulates other immune cells.
| S-EPMC6838076 | biostudies-literature